Ammonia → HCID 46216227, compound

Participants

Reaction Conditions

Reaction Steps

A heavy-walled vial was charged with (4-(3-bromopyridin-2-yloxy)phenyl)(1-(tetrahydro-2H-pyran-2-yl)-1H-benzo[d]imidazol-2-yl)methanone (0.150 g, 0.314 mmol), piperidine (0.041 mL, 0.470 mmol), cesium carbonate (0.204 g, 0.627 mmol), (r)-binap (0.020 g, 0.031 mmol), Pd3 dba3 (0.014 g, 0.016 mmol) and Toluene (4 mL). Nitrogen was bubbled into the flask for 5 mins. The vial was capped and heated to 80° C. After 12 hours, the reaction was partitioned with ethyl acetate and water. The organic layer was washed (2×) with an aqueous saturated solution of sodium bicarbonate, then with water and then brine. The organic layer was then dried with sodium sulfate and purified by column chromatography on silica gel using a gradient of 20 to 60% EtOAc in hexanes to give a clear residue. The residue was dissolved in MeOH (10 mL) and treated with 1 mL of TFA. The mixture was allowed to stir at room temperature. 10 ml of 2N ammonia in MeOH was added to the reaction with was reduced in vacuo. The residue was partitioned in water and EtOAc. The organic layer was washed (2×) with an aqueous saturated solution of sodium bicarbonate, then with water and then brine. The organic layer was then dried with sodium sulfate and reduced. The residue obtained was triturated in 1:1 ethyl acetate:ether and then dried in a vacuum oven to give product as solid. MS (ESI, pos. ion) m/z: 398.8 (M+1). IC50 (uM) ++++.

Provenance & Evidence